Effect of masoprocol on carbohydrate and lipid metabolism in a rat model of Type II diabetes

Extracts of the creosote bush (Larrea tridentata, family Zygophyllaceae) ha ve long been used as a folk remedy for Type II (non-insulin-dependent) diab etes by native Americans in southwestern North America. In this study we ha ve evaluated the metabolic effects of masoprocol, a pure compound isolated from the creosote bush, in a rat model of Type II diabetes. Animals were fe d a 20% fat (by weight) diet for 2 weeks prior to intravenous injection wit h streptozotocin (STZ, 0.19 mmol/kg). Diabetic animals (glucose 16-33 mmol/ l) were treated with vehicle, metformin (0.83 mmol/kg body weight) or masop rocol (0.83 mmol/kg body weight) twice a day for 4 days. Masoprocol treatme nt lowered glucose concentrations an average of 35% compared with vehicle ( 14.2 +/- 1.1 vs 21.7 +/- 1.0 mmol/l, p < 0.001), a reduction similar to met formin treatment (12.8 +/- 0.9 mmol/l), without any change in insulin conce ntration. Masoprocol treatment also lowered triglyceride concentrations 80% compared with vehicle (1.0 +/- 0.1 vs 4.8 +/- 0.3 mmol/l, p < 0.001), a re duction far greater than following metformin treatment (3.6 +/- 0.3 mmol/l) . Non-esterified fatty acid and glycerol concentration were decreased by ap proximately 65% by masoprocol compared with vehicle, a reduction approximat ely twice as great as seen with metformin (p < 0.001). The effect of masopr ocol on in vivo insulin-mediated glucose disposal was evaluated by infusing fat-fed/STZ rats with glucose (0.22 mmol.kg.min(-1)) and insulin (30 pmol. kg.min(-1)) for 5 h. In response to the infusion, steady-state plasma gluco se concentrations were reduced 30% in masoprocol-treated animals compared w ith vehicle controls (p < 0.05) with no change noted in rats treated with m etformin. The effect of masoprocol treatment was also tested in primary adi pocytes isolated from normal animals. Adipocytes treated with masoprocol (3 0 mu mol/l) had higher basal and insulin-stimulated glucose clearance than did adipocytes treated with vehicle (p < 0.05). These data show that masopr ocol decreases both plasma glucose and triglyceride concentrations in fat-f ed/STZ rats, presumably as a result of its ability to both increase glucose disposal and decrease lipolysis.